The article presents the results of a spatio-temporal analysis of the changes of the favorability of climatic conditions for the transmission of vivax malaria in the Moscow megacity and its surroundings during the period from 1977 to 2016. Using the historical temperature records at urban and rural weather stations, we calculated the key indicators of climate favorability for malaria transmission, viz. the sum of effective temperatures, the duration of the season of effective infectiveness, and a new integral index of climate favorability. We demonstrated a dramatic increase of all three indicators, which accelerated after 1984, and a high spatial heterogeneity among them. Due to the urban heat island effect, the degree of climatic favorability is especially high in the densely urbanized areas of Moscow megacity compared with the suburban and rural areas. Climatic conditions for vivax malaria in Moscow are better now than before. The season of effective infectiveness continues in the central part of the city for 25 days longer, and the integral index of climate favorability is 85% higher in comparison to mean values over the rural surroundings. The study contains an alert regarding the risk of malaria resurgence in the Moscow region in the case of the sufficient importation of cases from abroad.